1. Technical Field
The present invention relates to a concentration determination apparatus, a probe, a concentration determination method, and a program for non-invasively determining a concentration of a target component in an observed object in any of a plurality of light scattering medium layers in a living body.
This application claims the benefit of priority to Japanese Patent Application No. 2010-235927 filed on Oct. 20, 2010, the contents of which are incorporated herein by reference.
2. Description of the Related Art
All patents, patent applications, patent publications, scientific articles, and the like, which will hereinafter be cited or identified in the present application, will hereby be incorporated by reference in their entirety in order to describe more fully the state of the art to which the present invention pertains.
In recent years, diabetics in an age of gluttony continue to increase each year in Japan. Therefore, diabetics with nephritis also continue to increase each year. Patients suffering from chronic renal insufficiency also continue to increase by ten thousand each year, and currently number over 280 thousand.
Meanwhile, with the advent of an aging society, a demand for preventive medicine and the importance of personal metabolism management are rapidly increasing. In particular, blood sugar value measurement is important. Glucose metabolism in an early stage of diabetes can be evaluated by blood sugar value measurement. The blood sugar value measurement enables early treatment based on early diagnosis of the diabetes.
Traditionally, the blood sugar value measurement is performed by taking a blood sample from a vein of, for example, an arm or a fingertip and measuring enzyme activity for glucose in the blood. This method of measuring a blood sugar value has various problems, such as that taking a blood sample is complicated and painful, and poses a risk of infection. Further, a measurement tip for adhering blood is required. Thereby, there is a need for a non-invasive blood sugar value measurement method that does not require that a blood sample be taken.
As a method of continuously measuring a blood sugar value, equipment for continuously determining glucose corresponding to a blood sugar value in a state in which an injection needle is pushed into a vein has been developed in USA and is currently in clinical trials. However, since the injection needle is pushed into the vein, there are risks of the needle being left or infection during measurement of the blood sugar value.
There is a need for a blood sugar value measurement apparatus capable of frequently measuring a blood sugar value without taking a blood sample and having no risk of infection. Further, there is a need for a miniaturized blood sugar value measurement apparatus capable of being mounted simply and at any time.
Japanese Patent No. 3931638 and Japanese Patent No. 3994588 disclose an apparatus to which the general principle of spectroscopic analysis and measurement is applied using the principle of molecular light absorption as an apparatus for non-invasively measuring a blood sugar level by use of near-infrared continuous light.
This apparatus is intended to prevent an error from occurring in the determination of a biological component concentration under the influence of subcutaneous fat when the biological component concentration is determined by using an infrared spectrum of skin. More specifically, an apparatus irradiates near-infrared continuous light to the skin and calculates a glucose concentration from the light absorption amount.
In this method, a calibration curve representing a relationship among a glucose concentration, a wavelength of irradiated near-infrared light, and a light absorption amount is created in advance. Near-infrared continuous light is irradiated to the skin, and light returned from the skin is scanned in any wavelength band using, for example, a monochromator. A light absorption amount for each wavelength in the wavelength band is obtained, and the light absorption amount in each wavelength is compared with the calibration curve. Accordingly, a glucose concentration, i.e., a blood sugar value, in the blood is calculated.
Skin properties are classified from absorbance at a specific absorption wavelength of subcutaneous fat selected from a wavelength range of 1700 rim to 1800 nm, and a calibration equation is selected as an alternative characteristic of “skin thickness.”
Furthermore, a calibration equation is selected after the “skin thickness” is determined to be either equal to or greater than 1.2 mm or less than 1.2 mm by preliminarily estimating the distance between near infrared light receiving and emitting units as 650 μm, and the distance between the light receiving unit and the light emitting unit is selected as either 650 μm or 300 μm.
On the other hand, as biological diagnosis using near-infrared light, for example, a method is known in which absorption amounts of near-infrared light in main components of the skin are measured by biological tissue imaging using a time-resolved measurement method, and each ratio of the main components of the skin, for example, a glucose concentration corresponding to blood sugar, is obtained based on the absorption amounts.
Because the absorption amounts of the main components of the skin depend upon wavelengths, a general method is adopted to estimate the ratios of the main components of the skin by pre-creating a plurality of spectra varying with change factors having the influence on a quantitative determination of the main components of the skin at a plurality of ratios in multivariate analysis, comparing spectra of measurement results of absorption amounts of near-infrared light in the main components of the skin with the plurality of spectra described above, and choosing a consistent spectrum from these spectra.
However, it is not possible to measure only an absorption amount of light of a path passing through a specific depth in an apparatus for non-invasively measuring the blood sugar level by use of near-infrared continuous light in the related art. Therefore, it is not possible to accurately determine a glucose concentration corresponding to blood sugar in the main components of the skin at a specific depth.
The apparatus of Japanese Patent No. 3931638 has the following problems when skin properties are classified from absorbance at a specific absorption wavelength of subcutaneous fat by designating a depth from a skin surface to the subcutaneous fat as the “skin thickness,” for example, when the “skin thickness” is used as a substitute for a depth from the skin surface to the subcutaneous fat.
(1) The boundary between a dermis and a subcutaneous tissue of the skin is not uniform as the depth from the surface of the skin.
(2) The dermis has sweat glands for secreting fat and accumulates fat secretions.
(3) When skin properties are classified from absorbance at a specific absorption wavelength of the subcutaneous fat, it is difficult to distinguish the dermis and the subcutaneous fat because fat is included in cells of the dermis and interstitial fluid.
In general, if a biological component concentration is determined using an infrared spectrum of the skin, a depth from a skin surface of an optical path within the skin is generally estimated by a banana-shape characteristic determined by a distance between the light receiving unit and the light emitting unit. For example, the depth from the skin surface of the optical path is estimated to be 325 μm if the distance between the light receiving unit and the light emitting unit is 650 μm, and the depth from the skin surface of the optical path is estimated to be 150 μm if the distance between the light receiving unit and the light emitting unit is 300 μm.
However, in the apparatus of Japanese Patent No. 3931638, it is not possible to specify a portion of which a biological component concentration is determined using an infrared spectrum of the skin for the above-described reason, and therefore it is not possible to selectively measure absorbance in an optical path that passes through a specific portion, wherein stratum reticulare in which glucose is one of interstitial components in the dermis is designated as the specific portion.